Ineffective control of murine cytomegalovirus by IE1-specific cytotoxic T lymphocytes during protracted infection in the lung

Interstitial pneumonia caused by cytomegalovirus (CMV) is a fatal disease i n immunocompromised patients. In order to examine the defense mechanism aga inst the virus in the lung, we employed an intratracheal infection model in susceptible mice. In mice infected intratracheally with murine CMV, a prot racted infection was observed where infectious virus was detected up to 21 days of infection. During this prolonged infection, massive accumulation in the lung of CD8(+) T cells with activated phenotypes occurred and these CD 8(+) T cells showed direct ex vivo cytolytic activity against target cells pulsed with the nonamer peptide derived from IE1 protein of the virus, whic h has been shown to be the dominant epitope recognized by most of virus-spe cific CTL. Moreover, adoptive transfer of in vitro induced IE1 peptide-spec ific CTL line showed no anti-virus effect in the lung, although they were e ffective in the spleen. Hence, there is reason to assume the IE1-specific C TL induced in vivo or in vitro plays limited roles during the prolonged inf ection in the lung.